Trovafloxacin is a quinolone antibiotic having the structure:
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It is currently administered in the form of the mesylate salt. Trovafloxacin and its mesylate salt are disclosed and claimed in U.S. Pat. No. 5,164,402, incorporated herein by reference.
Trovafloxacin mesylate can exist in a number of polymorphic forms as disclosed in PCT/US95/07211 (which designates, inter alia, the United States), which has been published as WO 96/39406, and which is herein incorporated by reference. The polymorphs are also disclosed in the Analyst, June 1997, V. 122, pp. 549-552 as Polymorph I, Polymorph II, and the mesylate monohydrate. Polymorph II, in particular, is an anhydrate which is stated to be hydrophobically stable such that formulation problems of the active ingredient during tabletting or encapsulation operations are alleviated. Polymorph I, also an anhydrate, is disadvantageous in that it is reported to be substantially hygroscopic such that it picks up water from the atmosphere to form a monohydrate, a third form of trovafloxacin. Reference to polymorphs in this application utilizes the same nomenclature designations as in the Analyst article for the sake of continuity.
When formulating a compound into a tablet (or other) dosage form, one typically seeks, inter alia, a formulation which is storage stable at temperatures and relative humidity levels above those typically encountered. One may additionally seek other desirable properties in a formulation such as fast dissolution so that the tablet quickly dissolves and the medicine is available for absorption, and also properties such as good compressibility and high ductility, and ease of formulatability in general. Accordingly, good storage stability and fast dissolution were, inter alia, features that were sought as desirable characteristics for the instant invention.
Surprisingly, only a single diluent or filler among many tested provided good storage stability and dissolution in conjunction with good manufacturability.